阿伐可泮在65岁及以上抗中性粒细胞胞浆抗体相关性血管炎患者中的疗效和安全性：ADVOCATE试验数据的事后分析

Efficacy and safety of avacopan in patients aged 65 years and older with ANCA-associated vasculitis: a post hoc analysis of data from the ADVOCATE trial.

作者信息

Geetha Duvuru, Pagnoux Christian, Sattui Sebastian E, Merkel Peter A, Weiner Maria, Draibe Juliana, Faguer Stanislas, Bray Sarah, Gurlin Rachel E, Balcells-Oliver Monica, Bruchfeld Annette, Jayne David R

机构信息

Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Vasculitis Clinic, Division of Rheumatology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

出版信息

Rheumatology (Oxford). 2025 Mar 3. doi: 10.1093/rheumatology/keaf122.

DOI:10.1093/rheumatology/keaf122

PMID:40037556

Abstract

OBJECTIVES

To evaluate the efficacy and safety of avacopan in patients aged ≥65 years with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) in the phase 3 ADVOCATE trial of avacopan vs a prednisone taper, plus either rituximab or cyclophosphamide.

METHODS

In this descriptive, post hoc analysis, patients receiving avacopan or a prednisone taper were stratified by age. Key efficacy outcomes included the rate of remission at week 26 and sustained remission at week 52.

RESULTS

Of 160 patients aged ≥65, 109 were aged 65-74, and 51 were ≥75. Remission at week 26 was achieved in 71.7% vs 69.4% of patients aged 65-74 and 73.1% vs 72.0% aged ≥75 in the avacopan vs prednisone taper groups, respectively. Sustained remission at week 52 was observed in 65.0% vs 55.1% of patients aged 65-74 and 65.4% vs 56.0% aged ≥75. Relapse rates in the avacopan vs prednisone taper groups were 12.3% vs 18.8% and 3.8% vs 20.8% in the 65-74 and ≥75 subgroups, respectively. Improvements in eGFR and HRQoL were observed in both treatment groups. Use of avacopan compared with a prednisone taper was associated with a 61% and 49% reduction in mean glucocorticoid dose in the 65-74 and ≥75 subgroups, respectively, and lower glucocorticoid toxicity. The proportions of patients with adverse events were similar between treatment groups within each age subgroup.

CONCLUSION

These data support the efficacy and safety of an avacopan-based regimen to treat patients with GPA or MPA aged ≥65.

摘要

目的

在阿伐考帕与泼尼松减量联合利妥昔单抗或环磷酰胺对比的3期ADVOCATE试验中，评估阿伐考帕对年龄≥65岁的肉芽肿性多血管炎（GPA）或显微镜下多血管炎（MPA）患者的疗效和安全性。

方法

在这项描述性的事后分析中，接受阿伐考帕或泼尼松减量治疗的患者按年龄分层。主要疗效指标包括第26周的缓解率和第52周的持续缓解率。

结果

在160例年龄≥65岁的患者中，109例年龄在65 - 74岁之间，51例年龄≥75岁。在阿伐考帕组与泼尼松减量组中，65 - 74岁患者第26周的缓解率分别为71.7%和69.4%，≥75岁患者分别为73.1%和72.0%。第52周时，65 - 74岁患者持续缓解率分别为65.0%和55.1%，≥75岁患者分别为65.4%和56.0%。在65 - 74岁和≥75岁亚组中，阿伐考帕组与泼尼松减量组的复发率分别为12.3%和18.8%，以及3.8%和20.8%。两个治疗组的估算肾小球滤过率（eGFR）和健康相关生活质量（HRQoL）均有改善。与泼尼松减量相比，阿伐考帕的使用使65 - 74岁和≥75岁亚组的平均糖皮质激素剂量分别降低了61%和49%，且糖皮质激素毒性更低。各年龄亚组内治疗组间不良事件患者比例相似。